To assess the relationship between the increase of fecal calprotectin, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease markers in a group of patients with spondyloarthritis.
We evaluated ...patients who were at least 18-years-old and met the Assessment in Spondyloarthritis International Society (ASAS) criteria for spondyloarthritis or the New York modified criteria. We analyzed activity criteria, physical function, analytical criteria (human leukocyte antigen HLA B27, fecal calprotectin, presence of ASCA, among others) and demographic data.
We included 33 patients. All but one patient had normal ASCA values. We found statistical significance in the correlation of calprotectin with C-reactive protein (CRP) but not with other parameters. We also found a relationship between calprotectin levels and nonsteroidal anti-inflammatory drug (NSAID) intake (P=.001). We found no relationship between CRP levels and NSAID use. After discontinuation of NSAIDs for one month, we found no significant differences in calprotectin levels (P=.9).
Fecal calprotectin is elevated in patients with spondyloarthritis and correlates positively with CRP. Level of fecal calprotectin is not altered by NSAID use. The amount of ASCA present does not change and does not correlate with any clinical parameters in the study population.
Myelodisplastic syndrome (MDS) is an aging associated clonal hematopoietic disorder characterized by a bone marrow failure in which immature blood cells do not mature properly. Oxidative stress seems ...to play a role in its pathogenesis. Reactive oxygen species (ROS) regulation exert a control between self-renewal, proliferation and cell differentiation. Thus, ROS imbalance could lead to disease, especially in bone marrow where cells seems to be vulnerable to oxidative stress. Interestingly, high ROS levels have been observed in MDS, which has been correlated with a diminished survival. Several types of molecules can be directly affected by oxidative damage. However, the oxidation of proteins is of particular concern since it leads to aggregation, unfolding, or conformational changes that may confer a loss of structural or functional activity. As an altered proteome has also been described during MDS, in this study we have analyzed the pattern of oxidized protein associated to MDS. Moreover, we analyzed whether MDS patients could be beneficed by the antioxidant effects of Deferasirox therapy.
Protein carbonylation was analyzed in bone marrow (n=14; 8 MDS and 6 controls) by immunohistochemistry after derivatization of carbonyl compounds with 2,4-dinitrophenylhydrazine (DNPH) and specific antibody detection of the 2,4-dinitrophenyl hydrazones. Protein carbonylation was also studied in expanded erythroblasts during in vitro erythropoiesis (n=9; 5 MDS and 4 controls) by 1-D and 2-D immunoproteomics. p21 mRNA levels were analysed by qRT-PCR using Taqman probes in a Applied Biosystems 7500 RT-PCR System. β-glucuronidase gene was used as endogenous reference to normalize data. Differences in expression mean values between the groups were analyzed using T-student or Mann-Whitney U test.
Immunohistochemistry assays showed a higher level of carbonylation in MDS samples (Figure 1a). We observed carbonylation in the cytoplasm of myeloid cells, whereas erythroid cells remained negative in both, patients and controls. Interestingly, MDS patients treated with Deferasirox presented lower levels than non-treated patients. Further, to assess carbonylation in the erythroid precursors, we analyzed the pattern of carbonylated proteins in expanded erythroblasts. Again, a higher level was observed in MDS vs . control group, which was reverted after Deferasirox treatment (Figure 1b). Most carbonylated proteins ranged in a size between 40-250 KDa. A highly carbonylated 40 KDa band was detected in all analyzed SMD samples. As seen in the 2D immunoblots, these differences in carbonylation were caused by a limited number of proteins or aggregates, rather than to a large spectrum of proteins (Figure 1c). Finally, as oxidative stress signaling pathways could regulate the cell cycle by p53, we analyzed the expression of p21, a p53 target during stress response. Upregulation of p21 was significantly observed in MDS samples. Remarkably, this effect was reverted upon Deferasirox treatment (Figure 1d).
An altered protein carbonylation pattern of myeloid and erythroid lineages was observed in MDS patients. This boosted oxidative cellular environment seems to activate signaling pathways involving p21. Deferaxirox treatment partially reverted these oxidative lesions at cellular level.
*both authors have contributed equally
M.L. hold a postdoctoral Fellowship of the Spanish Ministry of Economy and Competitiveness (FPDI-2013-16409)
Display omitted
No relevant conflicts of interest to declare.
* A.R. and M.L. have contributed equally.
Myelodysplastic syndrome (MDS) is a clonal disease that arises from the expansion of mutated hematopoietic stem cells. Oxidative stress could play an ...important role in the pathology of MDS since a correlation has been observed between high ROS levels and decreased survival in MDS patients. In addition, the oxidation of proteins leads to their aggregation, change and conformational changes that can cause the loss of their functions. Due to alteration of the proteome has been described in patients with MDS, in this study we considered the discovery of protein carbonylation to analyze its oxidation pattern. In addition, as the oxidative stress signaling pathways can regulate the cell cycle through p53, we analyzed p21, an important p53 target during the stress response. Finally, the possible benefit of treatment with Deferasirox as antioxidant therapy was studied.
Carbonylation pattern was analyzed in the different cell lines (n = 14, 6 MDS, 4 reactive controls and 4 MDS + DFX) by immunohistochemistry by derivatization with 2,4-dinitrophenylhydrazine (DNPH) and detection with anti-DNP antibodies. The degree of protein carbonylation was studied, also by derivatization and detection with anti-DNP, in primary cells of erythroblasts expanded for 11 days, by one-dimensional and two-dimensional electrophoresis (n = 16; 7 MDS, 6 controls, 2 reactive controls and 1 MDS + DFX). Expression levels of p21 were analyzed by qRT-PCR (n=19; 8C, 8 MDS, 3DFX).
Immunohistochemical assays revealed a higher level of carbonylation in patients with MDS (Fig. 1a). Interestingly, Deferasirox-treated MDS patients had lower levels than non-treated patients (Fig. 1b). In addition, to evaluate the carbonylation in the erythroid precursors, the pattern of carbonylated proteins in the expanded erythroblasts was analyzed. Again, a higher level of MDS was observed compared to the control group, which was reversed after treatment with Deferasirox. Two-dimensional electrophoresis revealed that differences in carbonylation are due to a limited number of proteins or aggregates, rather than to a large spectrum of proteins. Finally, an increased p21 expression was observed in patients with myelodysplasia and, surprisingly, this effect was reversed with Deferasirox treatment.
Patients with MDS showed a differential protein pattern respect to control patients, both in the myeloid and erythroid series. The increase in oxidative stress in myelodysplastic patients seems to activate signaling pathways involving p21. Treatment with Deferasirox can reverse the level of oxidation and the increase of p21 in patients with MDS.
Martinez Lopez:Celgene: Research Funding, Speakers Bureau; Jansen: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.
Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of ...effectiveness, adverse events, or the patient’s decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.
Climate change is currently regarded as the greatest global threat to human health, and its health-related consequences take different forms according to age, sex, socioeconomic level, and type of ...territory. The aim of this study is to ascertain the differences in vulnerability and the heat-adaptation process through the minimum mortality temperature (MMT) among the Spanish population aged ≥65 years by territorial classification. A retrospective, longitudinal, ecological time-series study, using provincial data on daily mortality and maximum daily temperature across the period 1983-2018, was performed, differentiating between urban and nonurban populations. The MMTs in the study period were higher for the ≥65-year age group in urban provinces, with a mean value of 29.6 °C (95%CI 29.2-30.0) versus 28.1 °C (95%CI 27.7-28.5) in nonurban provinces. This difference was statistically significant (
< 0.05). In terms of adaptation levels, higher average values were obtained for nonurban areas, with values of 0.12 (95%CI -0.13-0.37), than for urban areas, with values of 0.09 (95%CI -0.27-0.45), though this difference was not statistically significant (
< 0.05). These findings may contribute to better planning by making it possible to implement more specific public health prevention plans. Lastly, they highlight the need to conduct studies on heat-adaptation processes, taking into account various differential factors, such as age and territory.
Axial spondyloarthritis: can all be classified? Moreno Ramos, Manuel José; Moreno Martinez, Maria José; Linares Ferrando, Luis Francisco
Reumatologia clinica,
2017 Jan - Feb, Letnik:
13, Številka:
1
Journal Article
Introduction: tibia diaphyseal fractures are among the most common fractures that occur in long bones, intramedullary nailing is accepted as a surgical choice since it maintains the vascularization ...of the bone, which is very sensitive to pseudoarthrosis and infection. Aim: To describe the clinical epidemiological characteristics of patients with diaphyseal fracture of the tibia that underwent surgery with intramedullary nailing at the Celia Sanchez Hospital. Method: an observational-descriptive-retrospective study was carried out, in 24 patients who received surgical treatment with intramedullary nailing in the Orthopedics and Traumatology service, in the period from 2017-2020, with a diagnosis of tibia diaphyseal fracture. The variables were: age, sex, origin, causes, fracture trace, complications and incorporation to social life. Results: the predominant age group was 31 and 40 years old (34 %), and male sex (63 %). Most patients were from urban areas (66.7 %); traffic accidents accounted for 84 %, the fracture tract of fractures was predominantly transverse (55 %), the presence of patients without complications (67 %) and the incorporation to the social life of patients in a period fewer than six months (75 %). Conclusions: most of the operated patients did not present complications, so they were able to incorporate into society in a short period, making this method an excellent surgical alternative for this traumatic condition.
To assess the relationship between the increase of faecal calprotectin, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease markers in a group of patients with spondyloarthritis.
We evaluated ...patients who were at least 18 years old and met the Assessment in Spondyloarthritis International Society (ASAS) criteria for spondyloarthritis or the New York modified criteria. We analysed activity criteria, physical function, analytical criteria (human leucocyte antigen HLA B27, faecal calprotectin, presence of ASCA, among others) and demographic data.
We included 33 patients. All but one patient had normal ASCA values. We found statistical significance in the correlation of calprotectin with C-reactive protein (CRP) but not with other parameters. We also found a relationship between calprotectin levels and nonsteroidal anti-inflammatory drug (NSAID) intake (P=.001). We found no relationship between CRP levels and NSAID use. After discontinuation of NSAIDs for one month, we found no significant differences in calprotectin levels (P=.9).
Faecal calprotectin is elevated in patients with spondyloarthritis and correlates positively with CRP. Level of faecal calprotectin is not altered by NSAID use. The amount of ASCA present does not change and does not correlate with any clinical parameters in the study population.
Valorar la relación entre la calprotectina fecal, ASCA y marcadores de enfermedad en espondiloartritis (Spa).
Se evaluaron pacientes≥18 años que cumplían criterios ASAS o criterios modificados de Nueva York. Se analizan criterios de actividad, función física, analíticos y datos demográficos.
Se incluyeron 33 pacientes. Todos excepto uno tenían valores normales de ASCA. Encontramos correlación significativa entre calprotectina y PCR pero no con otros parámetros, ni entre los niveles de calprotectina y la toma de AINE (p=0,001). Tampoco entre los niveles de PCR y el uso de AINE. Después de retirar los AINE no encontramos diferencias en los niveles de calprotectina (p=0,9).
La calprotectina fecal está elevada en pacientes con Spa y se correlaciona positivamente con la PCR. La elevación de la calprotectina fecal no se ve alterada por el uso de AINE. La cantidad de ASCA no cambia y no se correlaciona con ningún parámetro clínico en el estudio poblacional.
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